Prognostic significance of multidetector CT in normotensive patients with pulmonary embolism: results of the protect study.

BACKGROUND: In patients with acute pulmonary embolism (PE), rapid and accurate risk assessment is paramount in selecting the appropriate treatment strategy. The prognostic value of right ventricular dysfunction (RVD) assessed by multidetector CT (MDCT) in normotensive patients with PE has lacked adequate validation. METHODS: The study defined MDCT-assessed RVD as a ratio of the RV to the left ventricle short axis diameter greater than 0.9. Outcomes assessed through 30 days after the diagnosis of PE included all-cause mortality and 'complicated course', which consisted of death from any cause, haemodynamic collapse or recurrent PE. RESULTS: MDCT detected RVD in 533 (63%) of the 848 enrolled patients. Those with RVD on MDCT more frequently had echocardiographic RVD (31%) than those without RVD on MDCT (9.2%) (p<0.001). Patients with RVD on MDCT had significantly higher brain natriuretic peptide (269±447 vs 180±457 pg/ml, p<0.001) and troponin (0.10±0.43 vs 0.03±0.24 ng/ml, p=0.001) levels in comparison with those without RVD on MDCT. During follow-up, death occurred in 25 patients with and in 13 patients without RVD on MDCT (4.7% vs 4.3%; p=0.93). Those with and those without RVD on MDCT had a similar frequency of complicated course (3.9% vs 2.3%; p=0.30). CONCLUSIONS: The PROgnosTic valuE of CT study showed a relationship between RVD assessed by MDCT and other markers of cardiac dysfunction around the time of PE diagnosis, but did not demonstrate an association between MDCT-RVD and prognosis.

Vocal cord paresis and diaphragmatic dysfunction are severe and frequent symptoms of GDAP1-associated neuropathy.

Cranial nerve involvement in Charcot-Marie-Tooth disease (CMT) is rare, though there are a number of CMT syndromes in which vocal cord paralysis is a characteristic feature. CMT disease due to mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) has been reported to be associated with vocal cord and diaphragmatic palsy. In order to address the prevalence of these complications in patients with GDAP1 mutations we evaluated vocal cord and respiratory function in nine patients from eight unrelated families with this disorder. Hoarseness of the voice and inability to speak loudly were reported by eight patients and one had associated symptoms of respiratory insufficiency. Patients were investigated by means of peripheral and phrenic nerve conduction studies, flexible laryngoscopy, pulmonary function studies and polysomnography. Nerve conduction velocities and pathological studies were compatible with axonal CMT (CMT2). Flexible laryngoscopy showed left vocal cord palsy in four cases, bilateral cord palsies in four cases and was normal in one case. Restrictive respiratory dysfunction was seen in the eight patients with vocal cord paresis who were all chair-bound. These eight had confirmed phrenic nerve dysfunction on neurophysiology evaluation. The patient with normal vocal cord and pulmonary function had a less severe clinical course.This study shows that CMT patients with GDAP1 mutations develop severe disability due to weakness of limb muscles and that laryngeal and respiratory muscle involvement occurs late in the disease process when significant proximal upper limb weakness has developed. The early and predominant involvement of the left vocal cord innervated by the longer left recurrent laryngeal nerve suggests a length dependent pattern of nerve degeneration. In GDAP1 neuropathy, respiratory function should be thoroughly investigated because life expectancy can be compromised due to respiratory failure.

[Predictive value of chest X-ray and electrocardiographic abnormalities in patients with pulmonary embolism in relation to mortality and recurrences]. / Papel de las alteraciones radiográficas y del electrocardiograma en la predicción de mortalidad y recidivas en pacientes con embolia de pulmón.

BACKGROUND AND OBJECTIVE: Radiological and electrocardiographic (EKG) abnormalities are very frequent in patients with pulmonary embolism (PE). Our main objective was to evaluate, in patients with PE, whether any of those abnormalities was correlated with an increased risk of relapses or mortality until 3 months after the acute episode. PATIENTS AND METHOD: Multicenter observational study of patients included in the Venous Thromboembolic Disease Register (RIETE). Demographic, clinical, radiological and EKG data were collected from all patients. Statistics was made with the Pearson correlation and multiple linear regression analysis. RESULTS: We found a significant but non determinant association between mortality and the presence of radiological and/or EKG abnormalities and no relation between them and relapses of PE. CONCLUSIONS: Radiological or EKG manifestations could not predict relapses or mortality 3 months after PE in our patients.

Short-term clinical outcome after acute symptomatic pulmonary embolism.

Though studies have identified clinical variables that predict adverse events in patients with acute pulmonary embolism (PE), they have typically not differentiated short-term from long-term predictors. This multicenter prospective cohort study included consecutive outpatients with objectively confirmed symptomatic acute PE. We analyzed the incidence and time course of death, venous thromboembolism (VTE) recurrence, and major bleeding, and we compared event rates during short-term (first week) and long-term (3 months) follow-up after the diagnosis of PE. We also assessed risk factors for short-term mortality. During the first three months after diagnosis of PE, 142 of 1,338 (10.6%) patients died. Thirty-six deaths (2.7%) occurred during the first week after diagnosis of PE, and 61.1% of these were due to PE. Thirty-eight patients (2.8%) had recurrent VTE during the three-month follow-up, though none of the recurrences occurred during the first week after diagnosis of PE. During the three-month follow-up, major bleeding occurred in 48 patients (3.6%). Twenty-one (1.6%) major bleeds occurred during the first week of follow-up, and nine of these were fatal. Short-term mortality was significantly increased in patients who initially presented with systolic arterial hypotension (odds ratio [OR] 3.35; 95% CI, 1.51-5.41) or immobilization due to a medical illness (OR 2.89; 95% confidence interval [CI], 1.31-6.39). In conclusion, during the first week after the diagnosis of PE, death and major bleeding occur more frequently than recurrent VTE. Patients with systolic arterial hypotension and immobilization at the time of PE diagnosis had an increased risk of short-term mortality.

[Usefulness of basic tests in patients with pulmonary embolism]. / Utilidad de las pruebas básicas en el paciente con embolia pulmonar.

There are common, specific noninvasive and invasive tests for the diagnosis of pulmonary embolism (PE). Arterial blood gases, lung radiography and electrocardiography belong to the first group and should be performed in patients with suspected PE. Among the second group, D-dimer determination is essential. Ventilation-perfusion scintigraphy was formerly the most frequently used test but has been relegated to a second-line position by the development of multislice computed tomography (CT) angiography, which provides the possibility of simultaneously studying the lower limbs to detect deep venous thrombosis (DVT). SPECT and magnetic resonance imaging can be used as an alternative to multislice CT angiography, but there is less experience with these techniques. Transthoracic echocardiography has, above all, predictive value and lower limb ultrasonography is the most common non-invasive method to detect DVT. Invasive tests, the gold standard, are often unavailable and their use is therefore limited to selected patients. In conclusion, noninvasive management (clinical probability, D-dimer and multislice CT) is feasible in most patients with suspected PE.

Pulmonary venous thrombosis secondary to radiofrequency ablation of the pulmonary veins.

BACKGROUND: Pulmonary Vein Thrombosis (PVT) is a rare and underdiagnosed entity produced by local mechanical nature mechanisms, vascular torsion or direct injury to the vein. PVT has been described in clinical cases or small multicenter series mainly in relation to pulmonary vein stenosis, metastatic carcinoma, fibrosing mediastinitis, as an early surgical complication of lung transplantation lobectomy and radiofrequency ablation performed in patients with atrial fibrillation, although in some cases the cause is not known. CASE: We report the case of a 57 years old male with history of atrial fibrillation treated by radiofrequency ablation who was admitted in our center because of a two-week history of consistent pleuritic pain in the left hemithorax and low-grade hemoptysis and a lung consolidation treated as a pneumonia with antibiotic but not responding to medical therapy. In view of the poor evolution of the patient, computed tomography angiography was performed with findings of PVT and secondary venous infarction and anticoagulation therapy was optimized. At the end, pulmonary resection was performed due to hemorrhagic recurrence. CONCLUSION: PVT remains a rare complication of radiofrequency ablation and other procedures involving pulmonary veins. Clinical suspicion and early diagnosis is crucial because is a potentially life-threatening entity.

Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy.

OBJECTIVE: To assess the performance of two prognostic models in predicting short-term mortality in patients with pulmonary embolism (PE). SUBJECTS AND METHODS: We compared the test characteristics of two prognostic models for predicting 30-day outcomes (mortality, thromboembolic recurrences, and major bleeding) in a cohort of 599 patients with objectively confirmed PE. Patients were stratified into the PE severity index (PESI) risk classes I-V and the Geneva low-risk and high-risk strata. We compared the discriminatory power of both prognostic models. RESULTS: The PESI classified fewer patients as low risk (strata I and II) [36%; 216 of 599 patients; 95% confidence interval (CI), 32 to 40%] compared to the Geneva prediction rule (84%; 502 of 599 patients; 95% CI, 81 to 87%) [p < 0.0001]. Using either prediction rule, the low-risk groups showed statistically relevant 30-day mortality difference (PESI, 0.9%; 95% CI, 0.3 to 2.2; vs Geneva, 5.6%; 95% CI, 3.6 to 7.6) [p < 0.0001], although nonfatal recurrent venous thromboembolism or major bleeding rates were statistically similar (PESI, 2.8%; 95% CI, 0.6 to 5.0%; vs Geneva, 4.2%; 95% CI, 2.4 to 5.9%). The area under the receiver operating characteristic curve was higher for the PESI (0.76; 95% CI, 0.69 to 0.83) than for the Geneva score (0.61; 95% CI, 0.51 to 0.71) [p = 0.002]. CONCLUSIONS: The PESI quantified the prognosis of patients with PE better than the Geneva score. This study demonstrated that PESI can select patients with very low adverse event rates during the initial days of acute PE therapy and assist in selecting patients for treatment in the outpatient setting.

[A clinical prediction rule for identifying short-term risk of adverse events in patients with pulmonary thromboembolism]. / Escala de riesgo de eventos adversos a corto plazo en pacientes con tromboembolia pulmonar.

OBJECTIVE: To identify patients with a low short-term risk of complications following acute pulmonary thromboembolism. PATIENTS AND METHODS: A prospective multicenter study was conducted in 8 Spanish hospitals; 681 consecutive outpatients diagnosed with pulmonary thromboembolism were enrolled. Clinically significant variables were weighted using coefficients derived from a logistic regression model in order to optimize the diagnostic performance of a clinical prediction rule to predict the following complications within 10 days of acute pulmonary thromboembolism: death, recurrent thromboembolism, and major or minor bleeding. RESULTS: Forty-three patients (6.3%) had 51 complications. These included 33 deaths, 12 major bleeding episodes, and 6 minor bleeding episodes. The clinical variables used in the prediction rule were assigned the following scores: recent major bleeding episode and cancer with metastasis, 4 points each; creatinine levels of over 2 mg/dL, 3 points; cancer without metastasis and immobility due to a recent medical condition, 2 points each; and absence of surgery in the past 2 months and an age of over 60 years, 1 point each. A risk score of 2 or less, obtained by 47.8% of patients, indicated a low short-term risk of developing complications following pulmonary thromboembolism. The area under the receiver operating characteristic curve for the prediction rule was 0.75 (95% confidence interval [CI], 0.67-0.83). For this cutoff point, sensitivity was 82.9% (95% CI, 68.7-91.5) and the likelihood ratios for a positive and negative test result were 1.63 (95% CI, 1.39-1.92), and 0.35 (95% CI, 0.18-0.69), respectively. CONCLUSIONS: Our clinical prediction rule could be useful for identifying patients with a low risk of complications in the 10 days following acute pulmonary thromboembolism. Those patients would be eligible for consideration for outpatient treatment.

[Early complications in patients with pulmonary embolism]. / Complicaciones precoces en pacientes con embolia de pulmón.

BACKGROUND AND OBJECTIVE: Mortality, recurrences and hemorrhages are the most serious early complications of pulmonary embolism (PE). We intended to ascertain the frequency and mechanisms of complications within the first 10 days after PE was diagnosed. PATIENTS AND METHOD: We included patients suspected of suffering PE between December 2003 and August 2004 from 8 hospitals. We performed a multicenter observational prospective study of 8 Spanish hospitals with consecutive outpatients diagnosed with PE. Database of clinical variables: computerized Registry of Patients with Venous Thromboembolism (RIETE). Statistic analysis included chi2 and Student's t test to compare the 2 groups of patients (with and without complications). RESULTS: Six hundred eighty one patients were included, 336 men and 345 women (mean age 66 and 70, respectively). During the first 10 days, 33 (4.8%) of them died, and 22 (3.2%) had an hemorrhage yet no recurrences appeared. Previous immobilization and the presence of respiratory failure, cancer or renal failure were significantly associated with early complications while previous surgery and thoracic pain were not associated with those. CONCLUSIONS: Early complications and some of the associated factors were in agreement with published data. Other situations such as previous surgery or thoracic pain appeared to be protective factors.

Recurrence of venous thromboembolism in patients with recent gestational deep vein thrombosis or pulmonary embolism: Findings from the RIETE Registry.

INTRODUCTION: The aim of this study was to investigate the recurrence rate of venous thromboembolism (VTE) and the prevalence of major bleeding or death in patients with previous VTE in pregnancy and puerperium. Risk factors for VTE recurrence were also assessed. MATERIALS AND METHODS: We evaluated a cohort of patients enrolled in the international, multicenter, prospective Registro Informatizado de la Enfermedad Trombo-Embólica (RIETE) registry with objectively confirmed VTE. RESULTS: In the registry, 607 women were presenting with VTE that occurred during pregnancy or puerperium. The 2-year VTE recurrence rate was 3.3% (CI: 95 1.5-5.0%) and the recurrent VTE incidence rate was 2.28events/100 patients-year. Among the 16 cases of VTE recurrence 11 cases appeared during drug treatment while only five cases were diagnosed after therapy discontinuation. No significant difference was found in treatment duration among these two subgroups of VTE recurrence cases and women without recurrence. Furthermore, the use of thrombolytics and inferior vena cava filter in initial treatment was associated to an increased risk of VTE recurrence. CONCLUSIONS: The current study provides new insights on VTE recurrence rate in patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) that occurred in pregnancy or postpartum period. These findings can contribute to risk assessment of thrombotic burden, thereby allowing for better decision making regarding antithrombotic management in this clinical setting.

Comparison of four scores to predict major bleeding in patients receiving anticoagulation for venous thromboembolism: findings from the RIETE registry.

Stratification of the individual bleeding risk prior to initiation of anticoagulation in patients with acute venous thromboembolism (VTE) has the potential to assist clinicians in making decisions about the proper intensity and duration of antithrombotic therapy. It is unclear which of the validated and internationally accepted scores recommended for the achievement of this important task has the best predictive value. We compared the predictive value of four validated scores (by Landefeld, Beyth, Kuijer and Ruiz-Gimenez, respectively) for the development of major bleeding complications occurring in the first 3 months in patients with acute VTE treated with conventional anticoagulation. Based on the population of RIETE Registry (international registry of patients with acute VTE), we identified those patients presenting all the required prognostic variables, and then calculated the ability of each score for predicting the bleeding risk. Of 40,265 eligible patients, we identified 8,717 meeting the recruitment criteria. Overall, 0.9 % of patients experienced at least one episode of major bleeding within 90 days of the index event. The proportion of patients classified as having a low risk varied between 1.2 and 3.7 %, that of patients having an intermediate risk between 76 and 93 %, and that of patients classified as having a high risk between 6.1 and 18 %. The area under the receiver operating characteristic ranged between 0.55 and 0.60, the positive predictive value between 1.5 and 3.2, and the likelihood ratio between 0.72 and 1.59. In conclusion, all four scores show a very low ability to predict the bleeding risk in patients with acute VTE undergoing conventional anticoagulation.

Factors associated with elevated pulmonary arterial pressure levels on the echocardiographic assessment in patients with prior pulmonary embolism.

BACKGROUND: Factors associated with the detection of raised systolic pulmonary artery pressure (sPAP) levels in patients with a prior episode of pulmonary embolism (PE) are not well known. METHODS: We used the RIETE Registry database to identify factors associated with the finding of sPAP levels ≥50 mm Hg on trans-thoracic echocardiography, in 557 patients with a prior episode of acute, symptomatic PE. RESULTS: Sixty-two patients (11.1%; 95% CI: 8.72-14.1) had sPAP levels ≥50 mm Hg. These patients were more likely women, older, and more likely had chronic lung disease, heart failure, renal insufficiency or leg varicosities than those with PAP levels <50mm Hg. During the index PE event, they more likely had recent immobility, and more likely presented with hypoxemia, increased sPAP levels, atrial fibrillation, or right bundle branch block. On multivariate analysis, women aged ≥70 years (hazard ratio [HR]: 2.0; 95% CI: 1.0-3.7), chronic heart or chronic lung disease (HR: 2.4; 95% CI: 1.3-4.4), atrial fibrillation at PE presentation (HR: 2.8; 95% CI: 1.3-6.1) or varicose veins (HR: 1.8; 95% CI: 1.0-3.3) were all associated with an increased risk to have raised sPAP levels. Chronic heart disease, varicose veins, and atrial fibrillation were independent predictors in women, while chronic heart disease, atrial fibrillation, a right bundle branch block or an S1Q3T3 pattern on the electrocardiogram were independent predictors in men. CONCLUSIONS: Women aged ≥70 years more likely had raised sPAP levels than men after a PE episode. Additional variables influencing this risk seem to differ according to gender.

Echocardiographic assessment of pulmonary arterial pressure in the follow-up of patients with pulmonary embolism.

BACKGROUND: Echocardiography remains a clinically useful screening test for chronic thromboembolic pulmonary hypertension (CTEPH) in patients with a history of pulmonary embolism (PE). To devise an effective screening strategy, the definition of a high-risk group is necessary. METHODS: We examined a total of 744 patients with acute symptomatic pulmonary embolism (PE) who were enrolled in a Spanish multicenter study. Patients were monitored every 6months during the first two years, and then once a year thereafter. Transthoracic echocardiography was used to screen patients with a clinical suspicion of CTEPH during follow-up. Pulmonary arterial hypertension was defined as an estimated pulmonary artery systolic pressure (PAP)>50mm Hg. The index thromboembolic episode was considered severe if: (a) the patient was immobilized for medical reasons; or (b) systolic blood pressure was less than 90mm Hg; or (c) troponin T values were above the reference range. RESULTS: The incidence of PAP>50mm Hg at 36months was 8.3% (95% confidence interval=4.6%-14.5%). Statistical analysis showed a highly significant association between a severe index thromboembolic episode and the subsequent detection of PAP>50mm Hg on echocardiography, with high positive likelihood ratio (2.40) and negative predictive value (>0.97). CONCLUSIONS: Patients with a severe index thromboembolic episode would constitute a high-risk group for the development of CTEPH. This group of patients should be subjected to a strict follow-up protocol.

Home treatment in pulmonary embolism.

BACKGROUND: Limited data exist on the feasibility of providing outpatient care to patients with acute pulmonary embolism (PE). METHODS: We conducted a multicenter randomized clinical trial in acute symptomatic PE to compare the efficacy and safety of early discharge versus standard hospitalization. A clinical prediction rule was used to identify low-risk patients. All patients were followed for three months. The primary outcomes were venous thromboembolic recurrences, major and minor bleeding, and overall mortality. RESULTS: One hundred and thirty two low-risk patients with acute symptomatic PE were randomized to early discharge (n=72) or standard hospitalization (n=60). Overall mortality was 4.2% (95% CI, 0.5-8.9) in the early discharge group and 8.3% (95% CI, 1.1-15) in the standard hospitalization group (Relative Risk (RR) 0.5; 95% confidence interval [CI], 0.12-2.01). Non-fatal recurrences were 2.8% (95% CI, 1.1-6.6) in the early discharge group and 3.3% (95% CI, 1.3-8%) in the standard hospitalization group (RR 0.8; 95% CI, 0.12-5.74). The rates of clinically relevant bleeding were 5.5% in the early discharge group and 5% in the standard hospitalization group (P=0.60). Short-term mortality was 2.8% (95% CI, 0.8-9.6%) in the early discharge group as compared with 0% in the standard hospitalization group. Based on the rate of short-term death in a carefully selected population, the study was suspended. CONCLUSIONS: In spite of the number of complications in patients with acute symptomatic PE randomized to standard hospitalization or early discharge did not differ significantly. The rate of short-term mortality was unexpectedly high in a (a priori) low-risk group of patients with acute PE. The accuracy of clinical prediction scores needs to be validated in well designed clinical trials. (ClinicalTrials.gov number, NCT00214929.).